ArticleBlood cancer journal2014
Sensitivity of MLL-rearranged AML cells to all-trans retinoic acid is associated with the level of H3K4me2 in the RARα promoter region.
Article in Blood cancer journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- Synthesis and Binding Affinity Insights of 2-Phenyl-1H-Benzimidazole Inhibitors Targeting FTO by Spectroscopic Characterization and Molecular Docking.Journal of molecular recognition : JMR · 2026Article
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- Nanoparticle-encapsulated retinoic acid for the modulation of bone marrow hematopoietic stem cell niche.Bioactive materials · 2024Article
- Synergistic Effects of the RARCancers · 2024Article
- Differentiation of imatinib -resistant chronic myeloid leukemia cells with BCR-ABL-T315I mutation induced by Jiyuan Oridonin A.Journal of Cancer · 2023Article
- Co-existence of a novel translocation t(11;22)(q23;q12.1) with PML-RARA in acute promyelocytic leukemia: a case report.Annals of hematology · 2022Article
- Targeting histone methylation to reprogram the transcriptional state that drives survival of drug-tolerant myeloid leukemia persisters.iScience · 2022Article
- RXRA DT448/9PP generates a dominant active variant capable of inducing maturation in acute myeloid leukemia cells.Haematologica · 2022Article
- Dynamic regulation and functions of mRNA m6A modification.Cancer cell international · 2022Review
- All-trans retinoic acid induces differentiation in primary acute myeloid leukemia blasts carrying an inversion of chromosome 16.International journal of hematology · 2022Article
- KDM5A suppresses PML-RARα target gene expression and APL differentiation through repressing H3K4me2.Blood advances · 2021Article
- Immunotherapeutic Potential of m6A-Modifiers and MicroRNAs in Controlling Acute Myeloid Leukaemia.Biomedicines · 2021Review
- Clinical Responsiveness to All-trans Retinoic Acid Is Potentiated by LSD1 Inhibition and Associated with a Quiescent Transcriptome in Myeloid Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- IGFBP7 activates retinoid acid-induced responses in acute myeloid leukemia stem and progenitor cells.Blood advances · 2020Article
- The Potential Role of N6-Methyladenosine (m6A) Demethylase Fat Mass and Obesity-Associated Gene (FTO) in Human Cancers.OncoTargets and therapy · 2020Review
- Eradication of Central Nervous System Leukemia of T-Cell Origin with a Brain-Permeable LSD1 Inhibitor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Article
- Article
- Diptoindonesin G promotes ERK-mediated nuclear translocation of p-STAT1 (Ser727) and cell differentiation in AML cells.Cell death & disease · 2017Article
- FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a NCancer cell · 2017Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
All-trans retinoic acid (ATRA) is well established as differentiation therapy for acute promyelocytic leukemia (APL) in which the PML-RARα (promyelocytic leukemia-retinoic acid receptor α) fusion protein causes blockade of the retinoic acid (RA) pathway; however, in types of acute myeloid leukemia (AML) other than APL, the mechanism of RA pathway inactivation is not fully understood. This study revealed the potential mechanism of high ATRA sensitivity of mixed-lineage leukemia (MLL)-AF9-positive AML compared with MLL-AF4/5q31-positive AML. Treatment with ATRA induced significant myeloid differentiation accompanied by upregulation of RARα, C/EBPα, C/EBPɛ and PU.1 in MLL-AF9-positive but not in MLL-AF4/5q31-positive cells. Combining ATRA with cytarabine had a synergistic antileukemic effect in MLL-AF9-positive cells in vitro. The level of dimethyl histone H3 lysine 4 (H3K4me2) in the RARα gene-promoter region, PU.1 upstream regulatory region (URE) and RUNX1+24/+25 intronic enhancer was higher in MLL-AF9-positive cells than in MLL-AF4-positive cells, and inhibiting lysine-specific demethylase 1, which acts as a histone demethylase inhibitor, reactivated ATRA sensitivity in MLL-AF4-positive cells. These findings suggest that the level of H3K4me2 in the RARα gene-promoter region, PU.1 URE and RUNX1 intronic enhancer is determined by the MLL-fusion partner. Our findings provide insight into the mechanisms of ATRA sensitivity in AML and novel treatment strategies for ATRA-resistant AML.
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